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\begin{document}

\title{Controlling reaction rate of phase transfer hydrogenation of
acetophenone by application of low external electric field}



\author[1]{Nan Wang}%
\author[1]{Alan Allgeier}%
\author[1]{Laurence Weatherley}%
\affil[1]{University of Kansas}%


\vspace{-1em}



  
  \date{June 12, 2024}


\begingroup
\let\center\flushleft
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\maketitle
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\selectlanguage{english}
\begin{abstract}
The controllable mass transfer and reaction rate for phase transfer
hydrogenation of acetophenone across a well-defined boundary were
investigated. The effect of solvent was found important and 1-butanol
exhibited the best performance among the five investigated homologous
alcohol solvents, consistent with its higher solubility in water and
greater dielectric constant. Initial reaction rates increased with
increasing electric potential, consistent with enhanced mass transfer
across the aqueous/organic boundary. At longer reaction times
deactivation was apparent. It correlated with increasing voltage and is
ascribed to lower equilibrium concentration of reactive species at the
interface. External control over reaction rate was demonstrated by
switching the applied electric potential over the course of the
reaction. Effects of external electric field on enantioselectivity were
also explored with reversal field direction. The changes correlate with
catalyst decomposition.%
\end{abstract}%



\sloppy


\textbf{1. Introduction}

Controlling reaction rate and selectivity is a long-standing goal and
challenge in chemistry.\textsuperscript{1-3} Conventional ways to
control chemical reactions include heating,\textsuperscript{4} stirring,
using solvents\textsuperscript{5} or
catalysts.\textsuperscript{6}Recently, inspired by the pioneering work
of Shaik and co-workers,\textsuperscript{7-9} attention has turned to
the manipulation of activation energy barriers and the stabilization of
reactive species in chemical reactions by oriented external electric
fields (OEEFs).\textsuperscript{10,11} The influence of OEEFs upon
chemical reaction performance has raised a number of scientifically
interesting questions, and increasing evidence has shown that OEEFs
could be employed as smart reagents and catalysts in
chemistry.\textsuperscript{10,12-15} It was proposed by Meir et
al.\textsuperscript{8} that organic reactions can be theoretically
accelerated when an external electric field is oriented along the
``reaction axis'' which enhances the electron flow, leading to a lower
reaction barrier and the stabilization of transition states. This
simulated prediction was experimentally demonstrated by Aragones et al.
in an OEEF promoted Diels-Alder reaction at the single molecule
scale.\textsuperscript{16} Huang et al. also proved this idea by
selective catalysis of a Diel-Alder addition reaction with an external
electric field oriented along the reaction
coordinate.\textsuperscript{17} More importantly, Wang et al. predicted
that the reaction enantioselectivity may be controlled by aligning the
electric field along the dipole moment of the
reactants.\textsuperscript{2} While it is potentially significant for
asymmetric synthesis, there is no direct experimental evidence so far to
support it.

Despite the promising prospects, there are two major challenges to be
met in order to utilize OEEFs for controlling reaction rates and
selectivity. One requirement is to orient the electric field along the
reaction axis,\textsuperscript{10} the other is the high electric field
strength (10\textsuperscript{7} to
10\textsuperscript{9}V/m).\textsuperscript{17,18} At molecular level,
these challenges can be addressed by using scanning tunneling microscope
break junction (STMBJ) techniques\textsuperscript{16,19,20} or
mechanically controllable break junction (MCBJ)
techniques.\textsuperscript{17,21,22} Nevertheless, when conducting
experiments on a bulk scale, the question of how to align the electric
field along the reaction axis arises when thousands of reactant
molecules are randomly oriented in the reaction system. Furthermore,
applying thousands of volts to a lab-scale (or even larger scales)
reactor could pose safety issues. Therefore, the significance of OEEFs
on controlling reaction rates and selectivity experimentally in bulk
quantity reactions for organic synthesis remains understudied. However,
apart from lowering the reaction barrier with huge energy input, a
simple way to manipulate the reaction rates by external electric fields
is to control the diffusion of reactive species in the reaction
system,\textsuperscript{23} and alter the local concentration of
reactants.\textsuperscript{24} This has been validated in our previous
study that the reaction rate can be either promoted or inhibited by
simply flipping the orientation of the external electric
field.\textsuperscript{25}

To further explore the possibilities of controlling reaction rate and
even selectivity with external electric field on bulk scales, catalytic
transfer hydrogenation of acetophenone was studied in a biphasic liquid
system. Previous studies showed that the phase transfer hydrogenation of
acetophenone with sodium formate as hydrogen source is a mass transfer
limited reaction happening at the organic-aqueous
interface.\textsuperscript{25,26} When an external electric field was
applied, the charged reactive species could be either transferred to the
interface to promote the reaction or constrained in the corresponding
liquid phases decelerating the reaction by the electrostatic
forces.\textsuperscript{25} This raises the possibility of manipulating
the reaction rates by controlling the diffusion of reactive species in
the presence of varying electric field potential for interfacial
reaction/catalysis in a biphasic liquid system.

In this contribution, we have demonstrated the ability of external
electric fields to control reaction rates in the catalytic phase
transfer hydrogenation of acetophenone and its influence on reaction
enantioselectivity. Mathematical modeling and simulation results further
support the controllable migration of reactive species under external
electric fields. While evincing fundamental principles, the results also
show the possible decomposition effects of the external electric field
on the catalyst when applied in the negative orientation, resulting in
lower reaction conversion and enantioselectivity. In general, this work
shows the importance of comprehensively understanding the role of
external electric field in organic synthesis and catalysis on bulk
scale.

\textbf{2. Experimental section}

2.1 Materials

All chemicals used in this work were purchased from commercial reagent
suppliers and used without further purification: acetophenone
(Sigma-Aldrich, 99\%), sodium formate (Sigma-Aldrich, 99.0\%),
RuCl(p-cymene){[}(S,S)-Ts-DPEN{]} (Sigma-Aldrich), 1-butanol
(Sigma-Aldrich, 99.8\%), 1-pentanol (Sigma-Aldrich, [?] 99\%), 1-hexanol
(Alfa Aesar, 99\%), 1-heptanol (Sigma-Aldrich, 98\%), 1-octanol
(Sigma-Aldrich, [?] 99\%).

2.2 Experimental apparatus and procedure

The phase transfer hydrogenation of acetophenone to produce
1-phenylethanol was studied in a specially made hollow cylindrical glass
reactor with two ports for electrodes on the ends. The inner diameter of
the reactor is about 20 mm. Details of the experimental unit may be
found elsewhere.\textsuperscript{25} Briefly, the biphasic system was
set up with a sodium formate/water solution as the more dense aqueous
phase and acetophenone/organic solvents as the less dense organic phase
in which the Ru complex (RuCl(p-cymene){[}(S,S)-Ts-DPEN{]}) was
dissolved. The organic solvents used in conjunction with acetophenone
were 1-butanol, 1-pentanol, 1-hexanol, 1-heptanol, and 1-octanol. An
external electric field (DC voltage) from a high voltage power supply
(PASCO SF-9585A) was applied across the two phases without agitation.
Stainless steel or titanium electrodes were used. In a single
experimental study, 0.34 g of sodium formate was fully dissolved in 1.5
mL of deionized water, while 117 \selectlanguage{greek}µ\selectlanguage{english}L of acetophenone was mixed with 1.5
mL of organic solvent to dissolve 0.0064 g Ru catalyst. The reactions
were conducted at room temperature and pressure with positive or
negative electric field applied during reaction. The detailed
orientations of the electric field have been described
previously.\textsuperscript{25} A positive orientation in this work is
defined as the direction of the electric field when the anode is placed
in the organic phase with the cathode in the aqueous phase. The
conversion of acetophenone, total yield of 1-phenylethanol, and
enantioselectivity of (S)-1-phenylethanol were determined by gas
chromatography analysis.

2.3 Gas chromatography (GC) analysis

10 \selectlanguage{greek}µ\selectlanguage{english}L of liquid samples from the organic phase were withdrawn after each
reaction and diluted to 1.5 mL with methanol for gas chromatography
analysis. An Agilent 6890N gas chromatograph equipped with a
CP-Chirasil-Dex CB column (25m\selectlanguage{ngerman}×0.25 mm) and a flame ionization detector
was used to identify reaction products and determine enantioselectivity
under the following conditions: helium as carrier gas (3 mL/min), inlet
and detector temperature 250 °C, oven temperature 115°C.

2.4 Nuclear Magnetic Resonance (NMR) spectroscopy analysis

Four samples were prepared for NMR analysis. Sample 1 was prepared by
dissolving 5.8 mg of RuCl(p-cymene){[}(S,S)-Ts-DPEN{]} in 500 \selectlanguage{greek}µ\selectlanguage{english}L of
MeOH-d4 (Cambridge Isotopes). Sample 2 was obtained by dissolving 6.4 mg
of RuCl(p-cymene){[}(S,S)-Ts-DPEN{]} in a mixture of 1.5 mL 1-butanol
and 117 \selectlanguage{greek}µ\selectlanguage{english}L acetophenone. Samples 3 and 4 were collected from reactions
under positive and negative 15 V of electric potential respectively
after 24 h with titanium electrodes and 1-butanol as solvent. 500 \selectlanguage{greek}µ\selectlanguage{english}L of
each liquid sample were pipetted into a 5 mm NMR tube (Wilmad Lab-Glass,
Vineland, NJ). All NMR spectra were acquired on a 500 MHz Bruker AVIII
spectrometer equipped with a cryogenically cooled X-channel observe
probe. All data was analyzed using MestreNova NMR software (Santiago De
Compostela, Spain).

2.5 X-ray florescence (XRF) analysis

A handheld XRF analyzer (Olympus, Delta Professional) with Ru anode and
silicon drift detector was used for fast determination of the metal
contents in the degradation products of stainless-steel electrode. These
solid samples were collected from the interface after reaction and dried
prior for analysis. Precious metal mode with a targeted collimator was
employed during analysis. All samples were scanned three times and
analyzed with the workstation setup.

\textbf{3. Theoretical modeling and simulation}

The transport of the charged reactive species, referred to as
electromigration in the present study, was modeled based on the
Nernst-Plank equation.\textsuperscript{27-29} The molar flux of
species\emph{i} , \emph{J\textsubscript{i}} , is expressed in Equation
(1), describing the diffusion by concentration difference and migration
by electrostatic force. The convection term is not included due to the
fact that the experiments were conducted in a quiescent hydrodynamic
environment.

\(J_{i}=-D_{i}\nabla c_{i}-\frac{D_{i}z_{i}F}{\text{RT}}c_{i}\nabla\Phi\)(1)

where \emph{D\textsubscript{i}} is the diffusion coefficient
(m\textsuperscript{2}/s), \emph{c\textsubscript{i}} is the ion
concentration (mol/m\textsuperscript{3}), \emph{z\textsubscript{i}} is
the valence number, \emph{F} is the Faraday constant, \emph{R} is the
gas constant, \emph{T} is the absolute temperature (K), and \selectlanguage{greek}\emph{Φ} \selectlanguage{english}is
the electric potential (V). The Wilke-Chang equation was applied to
estimate the mutual diffusion coefficient if
necessary.\textsuperscript{30}

The electric field in the domain is described by the Poisson
differential equation\textsuperscript{30}:

\(\nabla\bullet(\varepsilon_{0}\varepsilon_{r}\nabla\Phi)={-\rho}_{v}\)(2)

where \selectlanguage{greek}\emph{ε\textsubscript{0}}\selectlanguage{english} is the dielectric constant of the free
space, \selectlanguage{greek}\emph{ε\textsubscript{r}}\selectlanguage{english} is the relative permittivity of
materials, \selectlanguage{greek}\emph{ρ\textsubscript{v}}\selectlanguage{english} is the electric space charge
density.

The equations were solved using finite element method in COMSOL
Multiphysics 5.4. Simulation was conducted to understand the mass
transfer of reactive species in the proposed reaction system, assuming
no reaction nor flux at/across the interface. Concentration profiles of
Ru catalyst and formate at the interface were calculated under various
external electric fields.

\textbf{4. Results and discussion}

4.1 Solvent effects

The effects of the different organic solvents used in conjunction with
the acetophenone reactant were first studied as their different physical
and chemical properties could significantly affect the reaction
performance, especially when an external electric field is applied. Five
primary alcohols, namely 1-butanol, 1-pentanol, 1-hexanol, 1-heptanol,
and 1-octanol as organic solvents were investigated due to their ability
to maintain a stable biphasic reaction system. The experimental results
are presented in Figure 1, showing total conversion values and product
yields. Table 1 lists the physical and chemical properties of the five
solvents. No corresponding aldehyde by-products were detected by GC
analysis after the reactions, which confirms the role of sodium formate
as hydrogen source and the concept of phase transfer hydrogenation. As
we can see, addition of 1-butanol resulted in the best performance on
promoting the transfer hydrogenation of acetophenone with conversion of
84.7\% and yield of 76.8\% after 24 h of reaction under 15 V of positive
DC voltage with stainless-steel electrodes. The conversion and yield
decreased gradually with the increase of the molecular weight of these
homologous alcohol solvents.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

\end{center}
\end{figure}

Figure 1. Acetophenone conversion (mol\%) and 1-phenelethanol yields
(mol\%) under 15V of positive external electric field for 24 h with
different organic solvents and stainless-steel electrodes.

One possible reason for the significantly different performance may be
their respective solubilities in water. Compared to the other solvents,
1-butanol has the highest solubility in water, which initially promotes
most of the interaction between the reactants at the interface,
resulting in the highest conversion and reaction rate (more than 2 fold
faster than that with 1-octanol as solvent). On the other hand, these
alcohols are protic solvents, which possess the ability to generate
protons by dissociation. With the largest dielectric constant among the
studied solvents, 1-butanol has the greatest potential to polarize and
generate protons under an external electric field. These protons could
further promote the dissociation of the neutral Ru compound
(RuCl(p-cymene){[}(S-S)-Ts-DPEN{]}) into the cationic Ru complex
(species \textbf{2} in Scheme 1) by removing the chloride
ion,\textsuperscript{31,32} therefore accelerating and promoting the
generation of the catalysts and ultimately increasing the production
rate. While the dipole moment and electrical conductivity might be
important in electrostatically promoted reactions according to our
previous investigation\textsuperscript{25} and Shaik and
coworkers,\textsuperscript{2} the differences of these properties
between the five solvents are small. Accordingly, it is difficult to
attribute the differences in reaction performance to dipole moment and
conductivity in the present study.

Table 1. Properties of the studied organic solvents.\selectlanguage{english}
\begin{longtable}[]{@{}lllll@{}}
\toprule
Solvent & Electrical conductivity (ns/cm) & Solubility in water
(25\selectlanguage{ngerman}°C/mass\%)\textsuperscript{33} & Dipole(D)\textsuperscript{33} &
Dielectric constant (20\selectlanguage{ngerman}°C)\textsuperscript{33}\tabularnewline
\midrule
\endhead
1-butanol & 36\textsuperscript{34,35} & 7.3 & 1.66 &
17.84\tabularnewline
1-pentanol & 41\textsuperscript{34,35} & 2.14 & 1.7 &
15.13\textsuperscript{a}\tabularnewline
1-hexanol & -- & 0.59 & -- & 13.03\tabularnewline
1-heptanol & -- & 0.164 & -- & 11.75\tabularnewline
1-octanol & 140\textsuperscript{36} & 0.046 & 1.76 & 10.3\tabularnewline
\bottomrule
\end{longtable}

a: This value was obtained at 25\selectlanguage{ngerman}°C.

4.2 Electric field potential

Various values of positive external electric field potential were
applied to determine its effects on mass transfer and kinetics in the
proposed reaction system. The conversion of acetophenone under different
positive external electric field strengths, recorded at different times
are shown in Figure 2. The data in this Figure are only for the
acetophenone/1-butanol mixture using stainless steel electrodes. It was
observed that the initial reaction rates increased with the increase of
the electric potential. The conversion of acetophenone in the presence
of an applied voltage of 100 V was observed to reach 44.5\% after a
reaction time of 2 hours, which is nearly 4 fold of the conversion
attained at 15 V. However, at longer reaction times, the rate of
increase was observed to decline. The decline was greater at the higher
voltages. For example, after 8 h, a higher conversion was achieved at 15
V compared to the values observed at 30 V and 50 V. The total conversion
at 15 V reached to 84.7\% after 24 h which is about 20\% higher than
that at 30 V and 40\% higher than that at 50 V.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image2/image2}

\end{center}
\end{figure}

Figure 2. Acetophenone conversion (mol\%) under different positive
external electric field for 24 h with stainless-steel electrodes and
1-butanol as solvent.

The increase in conversion with increased electric potential in the
first few hours is consistent with the role of external electric field
in controlling the reaction rates of the phase transfer hydrogenation
reaction by controlling mass transfer of the charged reactive species.
This is further supported by the simulation results in Figure 3. As we
can see, the rates of electromigration of both formate and Ru catalyst
were increased with the increase of voltage at the beginning. The
enhancement of reaction rate observed at higher electric field is
consistent with accelerated rates of transport of both formate anions
and the cationic Ru catalysts to the liquid-liquid interface, resulting
in more rapid reaction compared to that under lower electric potential.
The simulation results also suggested that the equilibrium concentration
of Ru catalyst at the interface is lower at higher voltage, which
explains the corresponding lower conversion at longer reaction times.
Additionally, a negatively charged alkoxide intermediate could be formed
during the reaction as suggested by Pavlova et
al..\textsuperscript{37}As the reaction continues, a portion of these
alkoxide anions could be attracted to the anode electrode and
constrained in the region close to it, preventing the reactive species
from interacting and retarding the reaction rates. This inhibition is
greater when a greater electrostatic force is applied, leading to the
lower reaction rate as observed at an elevated electric potential for
longer reaction times.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image3/image3}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image4/image4}

\end{center}
\end{figure}

Figure 3. Simulated concentration profiles at the interface under
various electric fields. (a) Concentration profile of formate ions, (b)
concentration profile of Ru catalyst.

On the other hand, an external electric field induced current flow in
the reaction system along with degradation of the anode electrode
(immersed in the organic phase) were observed. Additionally, gas bubbles
of unknown composition were generated on the cathode. The degradation of
the electrode was confirmed by weight loss measurement (see Cases 1, 2
and 3 in Table 2). The degradation products which formed a thin layer of
black slurry at the liquid-liquid interface were characterized by XRF
analysis. The analysis showed that the slurry consisted mainly of Fe,
Ni, and Cr with a small amount of Ru. For reactions under higher
electric potentials, higher current flows and greater degradation rates
of the electrode were observed as shown in Table 2 (Cases 1, 2, and 3).
The decomposition of the electrode is consistent with galvanic
corrosion, in which hydrogen is produced at the cathode with the
corrosion occurring at the anode. At higher electric potentials,
stronger galvanic corrosion effects would be expected, leading to
greater electrode degradation. With more metal ions released from the
degradation, higher current flows would be observed due to increased
conductivity of the liquid phase. The degradation products formed at the
interface could also contribute to the deceleration of the reaction by
inhibiting mass transfer to the catalyst at the interface. At higher
electric potential, a higher degradation was observed, leading to a
higher blocking coverage of the interface and finally achieving a lower
reaction rate and conversion.

To eliminate the negative effects of electrode degradation and clarify
the inhibiting effects of high electric potential, chemically stable
titanium electrodes were employed, and the results are recorded as Cases
4, 5, and 6 in Table 2, compared to those with stainless steel
electrodes (Cases 1, 2, and 3). For experiments with different electric
potential applied, the average degradation rate of titanium electrodes
is less than 0.1\% w/w, and no apparent black slurry was observed.
Although there was negligible evidence of electrode degradation of
titanium electrodes, reaction performance showed the same trend as
observed with stainless steel electrodes, when the applied electric
potential was increased. This suggests that the actual electrode
degradation plays a minimal role in changes in reaction performance,
thus strongly suggesting the controllable migration of Ru catalyst and
alkoxide ions under electrostatic force as being the main reason for the
reaction deactivation and the importance of external electric field in
controlling reaction rates. Furthermore, in spite of apparent reaction
deactivation, a constant product ((S)-1-phenylethanol)
enantioselectivity was achieved. This is further evidence that the
deactivation is most likely due to the controllable migration of
reactive species rather than catalyst decomposition.

A further set of experiments was conducted to investigate the reaction
performance when the applied electrical potential was varied over the
course of the reaction. With reference to Table 2, the data shown in the
last three rows list the results of these experiments, labelled Cases 7,
8, and 9. In case 7, after reacting for 8 h under 30 V, the electric
potential was switched to 15 V for 16 h, and the reaction yield reached
to 67.5\%, which is an increase of 7.4\% compared to that with solely 30
V applied for 24 h (Case 5). In case 8 and 9, 30 V or 50 V were applied
for 4 h respectively followed by 15 V applied for 20 h. In these two
cases, the yields of 1-phenylethanol increased when comparing to those
with solely 30 V or 50 V applied for 24 h. These results suggest that
the reaction could be externally controlled by simply switching the
applied electric potential over the course of the reaction.

Table 2. Summary for experiments under various positive external
electric fields.\selectlanguage{english}
\begin{longtable}[]{@{}llllllll@{}}
\toprule
Case & Voltage (V) & Time (h) & Electrode & Current (mA) & Weight loss
(\% w/w) & Yield (\%) & ee (\%)\tabularnewline
\midrule
\endhead
0 & 0 & 24 & -- & N/A & \textasciitilde{}0 & 49.8 & 94.6\tabularnewline
1 & 15 & 24 & SS & 1.2 & 3.5 & 76.8 & 93.5\tabularnewline
2 & 30 & 24 & SS & 1.7 & 4.3 & 55.5 & 93.4\tabularnewline
3 & 50 & 24 & SS & 2.6 & 4.4 & 32.6 & 93.3\tabularnewline
4 & 15 & 24 & Ti & 0.2 & 0.085 & 67.4 & 94.5\tabularnewline
5 & 30 & 24 & Ti & 0.5 & 0.085 & 60.1 & 94.5\tabularnewline
6 & 50 & 24 & Ti & 1.6 & 0.09 & 26.6 & 94.5\tabularnewline
7 & 30-8h + 15-16h & 30-8h + 15-16h & Ti & 0.2 & 0.09 & 67.5 &
94.5\tabularnewline
8 & 30-4h + 15-20h & 30-4h + 15-20h & Ti & 0.2 & 0.02 & 63.9 &
94.3\tabularnewline
9 & 50-4h + 15-20h & 50-4h + 15-20h & Ti & 0.2 & 0.1 & 47.1 &
94.3\tabularnewline
\bottomrule
\end{longtable}

4.3 Proposed mechanism

Based on the observations, a stepwise mechanism for the phase transfer
hydrogenation of acetophenone with aqueous formate as hydrogen source
and Ru-TsDPEN catalyst under an external electric field is proposed in
Scheme 1. The cationic Ru complex \textbf{2} is generated by removal of
chloride after compound \textbf{1} dissolves in 1-butanol. Following the
formation, species \textbf{2} undergoes electromigration to the
interface where a hydride is transferred to \textbf{2} from a formate to
generate catalyst \textbf{3} , with the release of
CO\textsubscript{2}.\textsuperscript{26} Instead of transferring both
hydrogen to the substrate concertedly,\textsuperscript{31} only the
hydride on Ru-H in catalyst \textbf{3} is transferred to acetophenone
with the proton on the NH\textsubscript{2} moiety
retained,\textsuperscript{37} resulting in the regeneration of
species\textbf{2} and the formation of the corresponding alkoxide
intermediate due to the stabilization of hydrogen bonding by
water.\textsuperscript{37} Finally, the alkoxide picks up a proton from
water to form the product,\textsuperscript{37} and the generated
hydroxide further reacts with CO\textsubscript{2} to form bicarbonate as
observed in our previous study.\textsuperscript{25}

\textbf{Hosted file}

\verb`image5.emf`  available at \url{https://authorea.com/users/332910/articles/459244-controlling-reaction-rate-of-phase-transfer-hydrogenation-of-acetophenone-by-application-of-low-external-electric-field}

Scheme 1. Proposed mechanism for the phase transfer hydrogenation of
acetophenone with aqueous formate as hydrogen source and Ru-TsDPEN
catalyst.

The stoichiometry and rate expression consistent with the proposed
mechanism are summarized in Equations (3) - (9), assuming that the
coordination of formate and decarboxylation are reversible and
equilibrated prior to hydrogen transfer,\textsuperscript{26}
where\emph{K} \textsubscript{1} is the equilibrium constant, and\emph{k}
\textsubscript{1}, \emph{k} \textsubscript{2},\emph{k} \textsubscript{3}
are the respective reaction rate constants.\emph{ACP} and
\emph{ACPH\textsuperscript{-}} represent acetophenone and its
corresponding alkoxide, while 1-\emph{PE} refers to 1-phenylethanol and
{[}\emph{Ru} {]} represents the total concentration of catalyst. As
CO\textsubscript{2} rapidly reacts with hydroxide during the reaction,
the concentration of CO\textsubscript{2} is expected to be small,
therefore the rate expression can be further simplified as a second
order kinetics over the concentration of catalyst and substrate
(Equation (9)). This is consistent with the study by Wu et
al.\textsuperscript{26} and with the above observation showing that the
reaction rates were limited by the concentration of Ru catalyst and the
alkoxide at the interface region. Both of these concentrations were
affected by the electromigration under the influence of external
electric fields. These observations suggest an important impact of
electric fields on kinetics of interfacial reactions involving reactive
ions.

\(2\ +\ \text{HCOO}^{\mathrm{-}}3\ +\ \text{CO}_{2}\) (3)

\(3\ +\ \text{ACP}2\ +\ \text{ACPH}^{\mathrm{-}}\) (4)

\(\text{ACPH}^{\mathrm{-}}\ +\ H_{2}O1-PE\ +\ \text{OH}^{\mathrm{-}}\)(5)

\(\text{CO}_{2}\ +\ \text{OH}^{\mathrm{-}}\text{HCO}_{3}^{\mathrm{-}}\)(6)

Overall:\(\text{HCOO}^{\mathrm{-}}\ +\ \text{ACP}\ +\ H_{2}O\rightarrow 1-PE\ +\ \text{HCO}_{3}^{\mathrm{-}}\)(7)

Rate expression:\(\text{\ \ \ \ \ \ r}\ =\ \frac{K_{1}k_{1}[Ru][ACP][\text{HCOO}^{\mathrm{-}}]}{[\text{CO}_{2}]\ +{\ K}_{1}[\text{HCOO}^{\mathrm{-}}]}\)(8)

When\([\text{CO}_{2}]\ll K_{1}[\text{HCOO}^{-}]\),\(r\ =\ k_{1}[Ru][ACP]\) (9)

4.4 Electric field polarity and product enantioselectivity

As shown in Table 2, the enantioselectivity of (S)-1-phenylethanol
remained constant with respect to electric field potential applied in
the positive orientation. Since the orientation of OEEF was proposed as
being important for controlling reaction selectivity, a reversed
external electric field was then applied to the reaction system. The
results are presented in Table 3. In these cases, the reaction was
inhibited when the electric potential was applied in the negative
orientation, which further confirms the hypothesis of controllable mass
transfer and reaction rates by external electric fields, in accord with
past findings. The yield of 1-phenylethanol increased with the increased
negative electric field strength, which was unexpected as a larger
inhibiting electrostatic force would be expected to result in a lower
reaction rate and conversion. This increase is likely due to the
significant increase on the current flow (Figure 4) in the reaction
system. Increase in current flow is consistent with the local
temperature increase due to joule heating, which would compete with the
inhibiting effects of higher negative electrostatic force and possibly
promote the reaction.

Table 3. Summary for experiments with various negative external electric
fields applied.\selectlanguage{english}
\begin{longtable}[]{@{}lllllll@{}}
\toprule
Voltage (V) & Voltage (V) & Time (h) & Electrode & Current (mA) & Yield
(\%) & EE (\%)\tabularnewline
\midrule
\endhead
0 & 0 & 24 & -- & N/A & 49.8 & 94.6\tabularnewline
-5 & 24 & 24 & Ti & -- & 16.9 & 91.0\tabularnewline
-10 & 24 & 24 & Ti & -- & 22.4 & 86.0\tabularnewline
-15 & 24 & 24 & Ti & -- & 23.0 & 66.1\tabularnewline
-20 & 24 & 24 & Ti & -- & 45.6 & 82.9\tabularnewline
-30 & 24 & 24 & Ti & -- & 48.4 & 75.2\tabularnewline
\bottomrule
\end{longtable}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image6/image6}

\end{center}
\end{figure}

Figure 4. Current flow at different reaction time under various negative
external electric fields.

On the other hand, with the increase of the inhibiting electric
potential, decreased (S)-1-phenylethanol enantioselectivities were
observed. However, these changes in the enantioselectivity are probably
not due to the ability of OEEF to control reaction selectivity but are
more likely attributed to the catalyst decomposition. Figure 5 showed
the NMR analysis for the identification of the structures of the
catalysts before and after reactions. Samples 1 (spectrum A) and 2
(spectrum B) were obtained by dissolving the Ru catalysts in
CD\textsubscript{3}OD and reaction mixture (1-butanol and acetophenone
mixture) respectively, and peaks from the Ru catalyst are clearly
present at approximately 6.57 and 6.79 ppm. For sample 3 (spectra C),
collected from the reaction run at positive 15 V for 24 h, small signals
(due to the low initial concentration and difficulty of detection in 1H
NMR spectra) for the Ru catalyst can be seen. However, the NMR spectra
for sample 4, from the reaction run at negative 15 V for 24 h, showed no
signals for the Ru catalyst. It remains unknown if the decomposition of
the Ru catalyst was caused by the negative external electric field, and
further investigation is required.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image7/image7}

\end{center}
\end{figure}

Figure 5. Stack plot of 1D 1H NMR spectra of samples 1 (A), 2 (B), 3 (C)
and 4 (D). To highlight the minor species, spectra B was expanded
vertically by 8 times, and spectra C and D were expanded by 24 times.

\textbf{5. Conclusion}

The reported work demonstrated experimentally controllable reaction
rates by low voltage external electric fields for the catalytic transfer
hydrogenation of acetophenone. The influence of applied electric
potential on reaction performance was evaluated experimentally and the
controllable mass transfer of reactive species by electric fields was
supported by simulation results. Significant improvements were shown at
low values of voltage relative to a control of zero volts, with an
optimum voltage of positive15 V. Increases beyond this value to positive
30 V and 50 V showed significant reduction in performance due to lower
equilibrium concentration of Ru catalyst at the interface and possible
formation and migration of the alkoxide intermediate during reaction.
The degradation products from the electrolytic corrosion of the
stainless-steel electrodes did not significantly impact the
hydrogenation reaction. The influence of different external electric
fields on the concentrations of reactive species at the interface was
suggested as the main reason for the differences in reaction
performance. Enantiomeric excess values were measured, and no
significant changes were observed with variation in the positive voltage
values. A mechanism and reaction rate expression were proposed based on
the observations, suggesting the importance of external electric fields
in reactions involving reactive ions.

The direction of the applied electric field was proved to be important
as both reaction conversion and enantioselectivity were significantly
reduced when the electric field was in the negative orientation. A
monotonic increase in conversion was observed as voltage increased from
negative 5 V to negative 50 V due to possible temperature increase
resulted from the increase of current. Catalyst decomposition by the
influence of negative voltages was concluded as the main reason for
reduced enantioselectivity, as implied from the NMR analysis.

Overall, this work extends the scope for controllable synthesis of
organic reactions conducted in two phase liquid systems and raises an
opportunity for green engineering with minimal energy consumption in the
proposed reaction system. It is also important for understanding the
influence of external electric fields on mass transfer and kinetics in
biphasic liquid systems used for organic synthesis and interfacial
catalysis on macroscale.

\textbf{Acknowledgements}

The work was supported by the Albert Learned Endowment from the
University of Kansas. The authors also would like to acknowledge Justin
T. Douglas for his assistance in the NMR analysis and Zachary R. Day for
his assistance in the XRF analysis.

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